Perfume and aroma enhancing compounds are widely used as additives in the detergent and food industries. These compounds are used, for example, to augment or enhance the aromas of certain detergent compositions and perfumes, or to enhance the aroma and flavor characteristics of certain food or tobacco products among other products. Compounds with floral, fruity, woody, or other pleasing aroma are particularly desirable.
Many of these compounds have specific molecular features, such as the presence of a cyclic ring and/or a ketone, ester or other carbonyl derivative. For example, many fragrance components may include a substituted cyclohexene structure. These structures include, for example, various isomers of ionone, isomers of damascone, isomers of cyclogeranate, and isomers of irone. Other cyclic fragrance compounds are also known.
The damascones, including α-damascone, β-damascone, and δ-damascone are examples of compounds having pleasing floral, fruity aromas used in the perfumery art. The damascone isomers differ in the position of the ring double bond as shown in Scheme 1.
For example, trans,trans-δ-damascone is one of the most widely used fragrance additives in the detergent and food industries. Therefore, the industrial scale production of δ-damascone and other related compounds is of great interest.
Ayyer et al., Journal of the Chemical Society Perkin Trans., 1975, 1, 1727-1736 discloses a 3-step synthesis of damascone starting from 1,3-pentadiene (piperylene) and mesityl oxide. The synthesis of the isomers of damascone involved three separate reaction processes, a Diels-Alder cycloaddition, epimerization of the resulting cyclohexenyl methyl ketone, and condensation/elimination with acetaldehyde in an aldol condensation process.
The Diels-Alder cycloaddition of piperylene as the diene and mesityl oxide as the dienophile forms a mixture of trans and cis-1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone (Equation 1). Prior art references utilize the Ayyer method or slight modifications thereof. Ayyer disclosed a Lewis acid (AlCl3) catalyzed Diels-Alder using conventional organic solvents (CH2Cl2), which affords the cyclohexene product in low yield (45%). Further optimization by other groups increased yields to 63% (U.S. Pat. No. 4,334,098 to Mookherjee et al.) using toluene as solvent. The cycloadduct is a mixture of the cis and trans ring isomers, with the cis-isomer of the cycloadduct predominating.

The prior art Lewis acid catalyzed Diels-Alder cycloadditions to form 1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone suffer from low yields and result in a mixture of cis and trans ring isomers. Further, the reaction requires a large excess of piperylene and aluminum chloride (AlCl3) and results in undesirable self polymerization of the piperylene diene. In addition, the use of aluminum chloride results in formation of aluminum hydroxide upon workup, resulting in handling and disposal problems of the aluminum hydroxide solid, particularly on an industrial scale. Isolation of the cycloadduct product also requires steam distillation, extraction, and fractional distillation to obtain a purified mixture of cis and trans-cyclohexene product. Finally, because of the high reaction dilutions, slow additions of reagents, large reaction vessels, long reaction times, and complex workup requirements, utilizing the conventional Diels-Alder cycloaddition technology on industrial scale is problematic.
Thus, for a commercially viable production of the isomers of damascone and other cyclohexane and cyclohexene based perfume components, rapid and efficient syntheses of cyclohexene intermediates, including for example, 1-(2,6,6-trimethylcyclohex-3-en-1-yl)ethanone, are necessary.